The long-term goal of the proposed research is to elucidate the mechanisms by which the genes command the establishment of neuronal circuits. We are especially interested in the genes which control the specificity of neuronal connectivity. We work with 30 identified neurons in Drosophila melanogaster. These are the neurons responsible for escape jump and flight. We already know much of the anatomy, physiology and connectivity of these neurons. In particular we know the role of each individual neuron in the generation of the starting jump and the precisely repeated cycle of activation of the flight motoneurons. We are now attempting to identify the genes which specify the properties and interconnections of these cells. We have developed behavioral and physiological screens to recover mutants in which these neurons are abnormal or abnormally connected. We analyze the effects of the mutations by light and electron microscopy, electrophysiology, genetic fate mapping and mosaic clonal analysis. By these methods we can determine the time and locus of normal gene action and the anatomical and electrophysiological defects caused by mutant gene action. This preparation is unique for the study of neuron-to-neuron connectivity because it combines the ability to do the sophisticated genetic manipulations that is only available in Drosophila with electrophysiology and electron microscopy, all on single identified cells.